磷酸组织胺诱导的Ⅰ型超敏反应对肝损伤作用的研究

目的:通过观察与Ⅰ型超敏反应相关的生物活性介质--组织胺对家兔肝脏有无直接损伤作用,进一步论证Ⅰ型超敏反应对肝脏的损伤作用.方法:选择34只家兔随机分为对照组、实验Ⅰ组和实验Ⅱ组3组;对照组只进行正常饲料喂养,实验Ⅰ组在正常饲料喂养的同时每天给予0.4μg/kg耳静脉注射磷酸组胺注射液,实验Ⅱ组在正常饲料喂养的同时每天给予0.08 μg/kg耳静脉注射磷酸组胺注射液;动态观察以上3个组的血清谷丙转氨酶(ALT)及血清谷草转氨酶(AST)变化;利用光学显微镜观察以上3个组肝组织的病理变化.结果:无论是实验Ⅰ组或实验Ⅱ组,经过一段时间的观察,发现血清内ALT和AST含量均显着高于对照组(P＜0.01),但Ⅰ、Ⅱ组之间无显着性差异(P＞0.05);实验Ⅰ组和实验Ⅱ组在显微镜下观察,其肝脏均有不同程的损伤和病理改变,且实验Ⅱ组的损伤和变化大于实验Ⅰ组,而对照组的肝脏则无明显的病理变化.结论:组织胺对家兔肝脏确实有一定的损伤作用,而且随着投予剂量和时间的增加,肝脏的损伤和病理变化也越显著;通过本研究,可以得出Ⅰ型超敏反应导致肝脏病理变化及损伤的见解.     

Induction of genotoxic damage is not correlated with the ability to methylate arsenite in vitro in the leukocytes of four mammalian species

Arsenic is a natural drinking water contaminant that impacts the health of large populations of people throughout the world; however, the mode or mechanism by which arsenic induces cancer is unclear. In a series of in vitro studies, we exposed leukocytes from humans, mice, rats, and guinea pigs to a range of sodium arsenite concentrations to determine whether the lymphocytes from these species showed differential sensitivity to the induction of micronuclei (MN) assessed in cytochalasin B-induced binucleate cells. We also determined the capacity of the leukocytes to methylate arsenic by measuring the production of MMA [monomethylarsinic acid (MMA(V)) and monomethylarsonous acid (MMA(III))] and DMA [dimethylarsinic acid (DMA(V)) and dimethylarsonous acid (DMA(III))]. The results indicate that cells treated for 2 hr at the G(0) stage of the cell cycle with sodium arsenite showed only very small to negligible increases in MN after mitogenic stimulation. Treatment of actively cycling cells produced induction of MN with increasing arsenite concentration, with the human, rat, and mouse lymphocytes being much more sensitive to MN induction than those of the guinea pig. These data gave an excellent fit to a linear model. The leukocytes of all four species, including the guinea pig (a species previously thought not to methylate arsenic), were able to methylate arsenic, but there was no clear correlation between the ability to methylate arsenic and the induction of MN.     

Determination of specific oxygen uptake rates in human hematopoietic cultures and implications for bioreactor design

Oxygen plays an important role in the cultivation of primary cellsex vivo. In this study, we used hermetically sealed tissue culture well inserts equipped with oxygen electrodes to measure the oxygen utilization of cultured human bone marrow mononuclear cells (BM MNCs). The oxygen uptake rate (OUR) of BM MNCs was determined during a 14-day culture in which both adherent and nonadherent cells were present. Early in the culture, the cells exhibited very low OURs. The specific OURs (uptake rate per cell) were at approximately 0.005 μmol/10⁶ cells/hr shortly after the initiation of culture. The OUR then increased as the cultures developed. After about 8 to 10 days of cultivation the specific OURs had increased to 0.038±0.006 and 0.025±0.005 μmol/10⁶ cells/hr for adherent and nonadherent cells, respectively, after which no further increase was observed. Based on these oxygen uptake rate data, a mathematical model of oxygen diffusion was formulated and use to investigate issues associated with hematopoietic bioreactor design, including initial cell density, medium depth, reactor configuration, and oxygen partial pressure.In situ OUR measurements confirmed predicted oxygen limitations based on the mathematical model and the experimentally determined OURs. High-density hematopoietic cultures present design challenges in terms of sufficient and uniform delivery of oxygen to an active hematopoietic culture. These challenges can be met by using parallelplate bioreactors with thin liquid layers.     

The role of mPer1 in morphine dependence in mice

Investigations using Drosophila melanogaster have shown that the circadian clock gene period can influence behavioral responses to cocaine, and the mouse homologues, mPer1 and mPer2, modulate cocaine sensitization and reward. In the present study, we applied DNAzyme targeting mPer1 to interfere the expression of mPer1 in CNS in mice and studied the role of mPer1 on morphine dependence. We found that the DNAzyme could attenuate the expression of mPer1 in CNS in mice. Mice treated with DNAzyme and morphine synchronously did not show preference to the morphine-trained side, whereas the control group did. In contrast, mice treated with DNAzyme after morphine showed preference to the morphine-trained side as well as the control group did. These results indicate that drug dependence seems to be influenced at least partially by mPer1, but mPer1 cannot affect morphine dependence that has been formed.     

敌枯双对雄性小鼠生殖细胞分裂比率及精原细胞染色体畸变的影响

本文研究丁敌枯双对BALB/C雄性小鼠生殖细胞分裂比率及精原细胞染色体畸变的影响。将实验小鼠随机分为三组,即实验组(敌枯双组),阳性对照组(环磷酰胺组)和阴性对照组(双蒸水组)。结果发现:敌枯双能明显诱发精原细胞多倍体率和裂隙率增加,抑制终变期/中期Ⅰ和中期Ⅱ细胞的减数分裂比率,促进精原细胞有丝分裂比率。实验结果还提示:在遗传毒理检测中亚急性实验是必要的,并对实验结果进行了初步讨论。     

Cervical tissue uptake of all-trans-retinoic acid delivered via a collagen sponge-cervical cap delivery device in patients with cervical dysplasia

The present study was undertaken to evaluate the systemic absorption and cervical tissue uptake of all-transretinoic acid (TRA), delivered via a collagen spongecervical cap delivery device in patients with intraepithelial cervical dysplasia. Ten patients with histologically proven mild or moderate cervical dysplasia were included in this pharmacologic study. The two TRA concentrations (0.05% and 0.372%) selected for study represent the starting and maximally tolerated doses used in phase I clinical trial. All-trans-retinoic-11-³H acid (³H-TRA, 500 Ci) was used to facilitate cervical tissue uptake studies. Cervical biopsies and post-treatment blood samples were obtained from each patient after TRA exposure. The uptake of TRA into cervical tissues four hours after drug administration was significantly increased at the maximally tolerated TRA dose. There was a rapid decrease in cervical tissue concentration of TRA at the 0.372% dose between 4 and 24 h after drug exposure, suggesting a relatively short elimination half-life of TRA in cervical tissues. HPLC analysis of post-treatment blood samples indicate that there was no systemic absorption of TRA after local cervical administration.     

非开胸食管内翻剥脱术

目的　研讨非开胸食管内翻剥脱的手术方法、优缺点及适应症。方法 :分析我院 1 992年至 2 0 0 0年 6月非开胸食管内翻剥脱胃重建食管术的 1 8例病历 ,其中下咽癌 5例、甲状腺鳞癌 1例、喉癌侵犯下咽者 4例、食管颈段癌 8例。结果 :本组病人食管床出血量均在 1 0 0ml以下 ,无吻合口漏等严重并发症 ,无手术死亡。结论 :本手术安全具有简便创伤小的优点 ,适用于颈段食管癌、下咽癌及甲状腺癌和喉癌侵及下咽者、部分早期食管癌和贲门癌。